Neurobehavioral development of neonatal rats after in-utero hypothyroxinemia: Efficacy of prenatal thyroxine treatment

The aim of this study was to assess the impact on neonatal neurobehavioral development of methimazole (MMI)-induced in-utero hypothyroxinemia and of correction by maternal-fetal thyroxine (T₄) transfer in the rat. Two groups of pregnant Sprague-Dawley rats received MMI as drinking water from gestation day 10 until birth. From day 16 until parturition, one of these groups received daily intraperitoneal injections of L-T₄ and the other received saline injections. A third (control) group drank tap water and received saline injections. From day of birth, offspring from all groups were raised by untreated foster darns. Their neurobehavioral development was monitored, on postnatal days 5-14 (N = 3/litter, from 30 litters) by experimenters blind to treatment group. Prenatal T₄ treatment resulted in correction of MMI-induced delayed appearance of three different reflexes. Body-weight gain of treated pups was similar to that of controls and more rapid than development of rats treated with MMI-alone. T₄ treatment did not prevent, however, MMI-induced delay in maturation of physiological landmarks (e.g. ear opening). At least a portion of the developmental delay resulting from prenatal (maternal) MMI administration may be reversed by maternal-fetal transfer of T₄ administered to the gravid dam.